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Updated: Aug 21, 2026
Functional Characterization and Visualization of Esophageal Fibroblasts Using Organoid Co-Cultures
Published on: January 6, 2023
Fibroblast heterogeneity in Peutz-Jeghers syndrome: identifying the polyp-driving subset†
1Department of Biochemistry, Faculty of Medicine, Toho University, Ota-ku, Tokyo, Japan.
Insights
Peutz-Jeghers syndrome (PJS) polyp formation is driven by specific fibroblasts producing interleukin-11 (IL-11). Neutralizing IL-11 significantly reduced polyp development in a mouse model, highlighting IL-11 as a potential therapeutic target for PJS.
Area of Science:
- Gastroenterology
- Oncology
- Cell Biology
Background:
- Peutz-Jeghers syndrome (PJS) is an inherited disorder linked to STK11 mutations, causing hamartomatous gastrointestinal polyps and impacting patient quality of life.
- The role of stromal cells in PJS polyp development is known, but their specific characteristics and contributions remain poorly understood.
Purpose of the Study:
- To identify the specific fibroblast population responsible for PJS polyp formation.
- To elucidate the molecular mechanisms by which STK11 deficiency leads to polyp development.
- To evaluate the therapeutic potential of targeting key mediators in PJS.
Main Methods:
- Identification and characterization of fibroblast populations enriched in PJS polyps.
- Analysis of secretory factors produced by these fibroblasts, focusing on interleukin-11 (IL-11).
- Investigation of the signaling pathways involved in STK11 deficiency and IL-11 expression.
- Assessment of IL-11 neutralization efficacy in a preclinical mouse model of PJS.
Main Results:
- Polyp-enriched crypt top fibroblasts (pCTFs) were identified as the pathogenic fibroblast population in PJS.
- STK11 loss in these cells leads to increased IL-11 expression, which promotes their pathogenic phenotype via autocrine signaling.
- A feedforward loop involving STK11 loss, IL-11 production, and pCTF activation was established.
- Neutralization of IL-11 significantly inhibited polyp formation in a PJS mouse model.
Conclusions:
- Interleukin-11 (IL-11) is a critical mediator linking STK11 deficiency to epithelial proliferation and PJS polyp formation.
- Targeting IL-11 presents a promising therapeutic strategy for preventing PJS polyp development.
- Further research into IL-11 neutralization for established polyps could refine preventive intervention strategies.
Abstract:
Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder caused by germline mutations in STK11, and is characterized by gastrointestinal hamartomatous polyps, the recurrent development of which significantly impacts patients' quality of life. While stromal cells have been implicated in PJS polyp formation, their specific characteristics remain unclear. Domènech-Moreno et al identify polyp-enriched crypt top fibroblasts (pCTFs) as the pathogenic fibroblast population and demonstrate that interleukin (IL)-11, a major secretory factor produced by these cells, serves as a critical mediator linking STK11 deficiency to epithelial proliferation. The study reveals that Stk11 loss triggers IL-11 expression, which in turn reinforces the pathogenic pCTF phenotype through autocrine signaling, forming a feedforward loop. Importantly, IL-11 neutralization significantly reduces polyp formation in a faithful mouse model, providing strong preclinical evidence for therapeutic translation. This work represents a significant advance in our understanding of PJS pathogenesis and establishes IL-11 as a promising therapeutic target. Future investigations into the effects of IL-11 neutralization on established polyps will further refine the translational potential of these findings for preventive intervention strategies. © 2026 The Pathological Society of Great Britain and Ireland.
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